Red blood cells Flashcards
what 2 things do HSCs have the ability to do
self renew- some daughter cells remain as HSCs , pool of HSC is non depleting
differentiate to mature progeny
which 3 places does haematopoiesis occur in embryonic devel and during which weeks of gestation
Yolk Sac 3 weeks, HSC is generated
Liver 6-8 weeks, HSC is maintained and expanded
Bone marrow in pelvis femur and sternum (for adult) 10 weeks, HSC begins haematopoietic activity
what type of molecule haematopoietic growth factors
what do they do
glycoprotein hormones that bind to cell surface receptor
regulate function of mature red blood cells
regulate the proliferation and differentiation of red blood cells
what are the growth factors for:
- red blood cell
- granulocyte
- monocyte
erythropoietin
G- CSF and cytokines
G-M CSF and cytokines
4 stages of the differentiation of red blood cells
myeloid progenitor
pro erythroblast
erythroblast
erythrocyte
- What are the 4 things required for erythropoiesis?
- What causes microcytic anaemia?
- What causes macrocytic anaemia?
Folate, B12, Iron, Erythropoietin
iron deficiency
B12 and folate deficiency
- What is erythropoietin and when would it stimulate bone marrow produce RBCs?
- What are the major functions of iron?
glycoprotein that regulates erythropoiesis
in response to hypoxia- low 02 in kidney, stimulate erythropoiesis to increase 02
transport 02 in Hb (haem iron)
Mitochondrial proteins cytochrome a,b,c for production of ATP
cytochrome P450 for hydroxylation reactions (eg drug metabolism)
- List 3 signs that may indicate a person has iron deficiency.
- What is the best absorbed form of iron
- Why is excess iron bad?
Koilonychia - spoon shaped nails
Glossitis - inflammation of tongue
Angular stomatitis - inflammation of corners of mouth
Ferrous Iron (2+)
no physiological excretion method
- What regulates the absorption of iron in the gut and what suppresses its synthesis?
- what does it do?
- what is it secreted in response to
Hepcidin, Erythropoietic activity
absorption (from stomach) and release of storage iron (from liver) is blocked by hepcidin
High storage iron
- What does non-haem iron require action of for absorption?
- What are folate and VB12 needed for?
- What does vitamin B12 bind to in the stomach during its absorption?
ascorbic acid/ vitamin C
to synthesis thymine
as they are needed to synthesis DTTP, its precursor
Intrinsic factor, the B12-IF complex binds to receptors in ileum
- Where is intrinsic factor made?
- What is pernicious anaemia?
- A lack of which foods in diet can lead to a vitamin B12 deficiency?
Gastric parietal cells
Lack of IF secretion
meat and fish
- Where does the absorption of folate take place?
- When do the requirements of folate increase?
- How long do red cells circulate for?
Duodenum
pregnancy, low RBC production eg sickle cell anaemia
120days
- Where do red cells undergo phagocytosis?
- What is released from the haem (porphyrin) ring when it is recycled?
- What is iron bound to on its way back to the bone marrow?
Spleen
Iron
Transferrin
- What does the catabolism of haem produce and where is this product excreted?
- Describe the red cell membrane
- What happens to red blood cells during hereditary spherocytosis?
Bilirubin
excreted in Bile
contains transmembrane proteins
has a lipid bilayer supported by protein cytoskeleton
These help to maintain flexibility and shape and elasticity/deformability of red blood cell
become spherical with no central pallour
- What causes these hereditary spherocytosis?
- What happens to those red blood cells?
vertical linkages are disrupted
loss of membrane without loss of cytoplasm, cell forced to round up
RBC is less flexible
haemolysis, they are prematurely removed by the spleen
- What causes hereditary elliptocytosis?
- What is a haem group made of?
- What is the difference in composition between adult and foetal haemoglobin?
a lack of iron disrupts horizontal linkages
Fe2+ and a polyphyrin ring
Adult- 2 alpha and 2 beta
Foetal- 2 Alpha and two Gamma
- Explain the Bohr Effect?
- Which shift of the sigmoid curve showing saturation of Hb at different ppO2 does Foetal Hb give?
- What is co-operativity?
High C02 so a low PH
easier offloading of oxygen at respiring tissues
left shift
when one 02 binds to haem which makes it easier for another 02 to bind, due to a change in the structure of haem
- What is 2,3-DPG and how does it work?
- What are Heinz Bodies?
Organic phosphate product, decreases O2 affinity of Hb by binding to Hb in response to anaemia, hypoxia and high altitude
Irregularly contracted cells due to oxidant damage to cell membrane Cells are irregular in outline, smaller than normal cells and have lost central pallor Hb is denatured and form round inclusions. called heinz bodies
what is ferrous iron derived from
what is ferric iron (3+)
Haem iron- animal derived, best absorbed form
non haem iron, from plant foods, requires action of reducing substances eg Vit C for absorption. some sources eg soy contain phytates which reduce absorption
what does erythrocyte function depend on
how does its shape help its function
membrane integrity
haemoglobin structure and function
cellular metabolism
biconcave- allow for manoeuvrability through small blood vessels
- What does deficiency of G6PD cause?
- what shunt is G6DP part of?
- What genetic inheritance pattern is it
- Where are oxidants from
RBCs more vulnerable to oxidant damage, usually causes intermittent severe intravascular haemolysis as a result of exposure to infection or oxidant damage
it is part of the hexose monophosphate shunt, which is tightly coupled to glutathione metabolism, which protects the red blood cell from damage
X inherited
in blood stream eg during infection or exogenous eg drugs or broad beans
what is RBC metabolism highly adapted to
how is it adapted
adapted to generate enough ATP to meet energy requirements
maintains:
membrane integrity and deformability
RBC volume
haemoglobin function
what does erythrocyte function depend on
membrane integrity
haemoglobin structure and function
cellular metabolism